Metalloproteins as a class are proteins having a metal ion complexed with the protein molecule at the protein's metal binding site. The metal ion contributes to the protein's function by a variety of chemical mechanisms including stabilizing protein structure, facilitating electron transfer in oxidation or reduction reactions, and the like.
The stereochemistry of metal ion complex structure in association with protein has been extensively characterized. Studies of known metalloproteins have resulted in the characterization of many metal ions that participate in metal-protein complexes, which help to identify the nature of the metal-protein complex. Three dimensional structures of metalloproteins based on xray crystallographic data are available for numerous metalloproteins and provide further insight into the nature of the metal-protein complex.
Freeman et al., Adv. Protein Chem., 22:257-424 (1967), has described the preparation of synthetic metal binding sites on polypeptides. Alterations of existing metalloproteins have been reported in which amino acid residues that participate in the metal-protein complex were substituted, resulting in changes in the apoprotein's metal ion specificity and in the binding constant for the metal ion. However no protein structure has been sufficiently characterized to allow reproducible protein engineering to form a metal binding site in a protein to provide the benefits of a metal cofactor to a protein.